RESUMO
The dynamics of uterine endometrium is important for successful establishment and maintenance of embryonic implantation and development, along with extensive cell differentiation and proliferation. The tissue event is precisely and complicatedly regulated as several signaling pathways are involved including two main hormones, estrogen and progesterone signaling. We previously showed a novel signaling molecule, Serine/threonine protein kinase 3/4 (STK3/4), which is responded to hormone in the mouse uterine epithelium. However, the role and regulation of its target, YES-associated protein (YAP) remains unknown. In this study, we investigated the expression and regulation of YAP in mouse endometrium. We found that YAP was periodically expressed in the endometrium during the estrous cycle. Furthermore, periodic expression of YAP was shown to be related to the pathway under hormone treatment. Interestingly, estrogen was shown to positively modulate YAP via endometrial epithelial receptors. In addition, the knockdown of YAP showed that YAP regulated various target genes in endometrial cells. The knockdown of YAP down-regulated numerous targets including ADAMTS1, AMOT, AMOTL1, ANKRD1, CTNNA1, MCL1. On the other hand, the expressions of AREG and AXL were increased by its knockdown. These findings imply that YAP responds via Hippo signaling under various intrauterine signals and is considered to play a role in the expression of factors important for uterine endometrium dynamic regulation.
Assuntos
Estrogênios , Proteínas Serina-Treonina Quinases , Útero/metabolismo , Proteínas de Sinalização YAP/metabolismo , Animais , Estrogênios/metabolismo , Feminino , Camundongos , Progesterona/metabolismo , Proteínas Serina-Treonina Quinases/genética , Transdução de SinaisRESUMO
The uterus is essential for embryo implantation and fetal development. During the estrous cycle, the uterine endometrium undergoes dramatic remodeling to prepare for pregnancy. Angiogenesis is an essential biological process in endometrial remodeling. Steroid hormones regulate the series of events that occur during such remodeling. Researchers have investigated the potential factors, including angiofactors, involved in endometrial remodeling. The Hippo signaling pathway discovered in the 21st century, plays important roles in various cellular functions, including cell proliferation and cell death. However, its role in the endometrium remains unclear. In this review, we describe the female reproductive system and its association with the Hippo signaling pathway, as well as novel Hippo pathway genes and potential target genes.
Assuntos
Endométrio , Via de Sinalização Hippo , Implantação do Embrião/fisiologia , Endométrio/metabolismo , Ciclo Estral/fisiologia , Feminino , Humanos , Gravidez , Útero/metabolismoRESUMO
Beta2-microglobulin (B2M) is a subunit of human leukocyte antigen class-I (HLA-I) heterodimer that mediates immune rejection through activation of cytotoxic T cells. B2M binding to HLA-I proteins is essential for functional HLA-I on the cell surface. Here, we generated a B2M homozygous knockout somatic cell nuclear transfer-induced embryonic stem cell (SCNT-ESC) line using CRISPR/Cas9-mediated gene targeting. B2M KO cell line, which does not express HLA-I molecules on cell surface, has pluripotency and differentiation ability to three germ layers. This cell line provides a useful cell source for investigating immunogenicity of allogeneic ESCs and their derivatives for tissue regeneration.
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Cluster of differentiation 73 (CD73, also known as ecto-5'-nucleotidase) is an enzyme that converts AMP into adenosine. CD73 is a surface enzyme bound to the outside of the plasma membrane expressed in several cells and regulates immunity and inflammation. In particular, it is known to inhibit T cell-mediated immune responses. However, the regulation of CD73 expression by hormones in the uterus is not yet clearly known. In this study, we investigated the expression of CD73 in ovariectomized mice treated with estrogen or progesterone and its regulation in the mouse uterus during the estrous cycle. The level of CD73 expression was dynamically regulated in the uterus during the estrous cycle. CD73 protein expression was high in proestrus, estrus, and diestrus, whereas it was relatively low in the metestrus stage. Immunofluorescence revealed that CD73 was predominantly expressed in the cytoplasm of the luminal and glandular epithelium and the stroma of the endometrium. The expression of CD73 in ovariectomized mice was gradually increased by progesterone treatment. However, estrogen injection did not affect its expression. Moreover, CD73 expression was increased when estrogen and progesterone were co-administered and was inhibited by the pretreatment of the progesterone receptor antagonist RU486. These findings suggest that the expression of CD73 is dynamically regulated by estrogen and progesterone in the uterine environment, and that there may be a synergistic effect of estrogen and progesterone.
Assuntos
5'-Nucleotidase/metabolismo , Estrogênios/farmacologia , Ciclo Estral/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Progesterona/farmacologia , Útero/metabolismo , 5'-Nucleotidase/genética , Animais , Ciclo Estral/efeitos dos fármacos , Feminino , Camundongos , Camundongos Endogâmicos ICR , Progestinas/farmacologia , Útero/efeitos dos fármacosRESUMO
Fumonisin B1 (FB1) structurally resembles sphingolipids and interferes with their metabolism leading to sphingolipid dysregulation. We questioned if FB1 could exacerbate liver or kidney toxicities in glutathione peroxidase 1 (Gpx1) and catalase (Cat) knockout mice. While higher serum levels of thiobarbituric acid reactive substances (TBARS) and sphinganine (Sa) were measured in Gpx1/Cat knockout mice (Gpx1/Cat KO) than wild type mice after 5 days of FB1 treatment, serum levels of alanine aminotransferase (ALT), sphingosine-1 phosphate (So-1-P), and sphinganine-1 phosphate (Sa-1-P) were found to be relatively low. Although Sa was highly elevated in Gpx1/Cat KO mice and wild mice, lower levels of So and Sa were found in both the kidney and liver tissues of Gpx/Cat KO mice than wild type mice after FB1 treatment. Paradoxically, FB1-induced cellular apoptosis and necrosis were hastened under oxidative stress in Gpx1/Cat KO mice.
RESUMO
Cellular senescence of endothelial cells causes vascular dysfunction, promotes atherosclerosis, and contributes to the development of age-related vascular diseases. Sirtuin 6 (SIRT6), a conserved NAD+-dependent protein deacetylase, has beneficial effects against aging, despite the fact that its functional mechanisms are largely uncharacterized. Here, we show that SIRT6 protects endothelial cells from senescence. SIRT6 expression is progressively decreased during both oxidative stress-induced senescence and replicative senescence. SIRT6 deficiency leads to endothelial dysfunction, growth arrest, and premature senescence. Using genetically engineered endothelial cell-specific SIRT6 knockout mice, we also show that down-regulation of SIRT6 expression in endothelial cells exacerbates vascular aging. Expression microarray analysis demonstrated that SIRT6 modulates the expression of multiple genes involved in cell cycle regulation. Specifically, SIRT6 appears to regulate the expression of forkhead box M1 (FOXM1), a critical transcription factor for cell cycle progression and senescence. Overexpression of FOXM1 ameliorates SIRT6 deficiency-induced endothelial cell senescence. In this work, we demonstrate the role of SIRT6 as an anti-aging factor in the vasculature. These data may provide the basis for future novel therapeutic approaches against age-related vascular disorders.
Assuntos
Envelhecimento/metabolismo , Senescência Celular , Células Endoteliais/metabolismo , Proteína Forkhead Box M1/metabolismo , Sirtuínas/metabolismo , Animais , Regulação para Baixo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Sirtuínas/genéticaRESUMO
Baculoviral inhibitor of apoptosis repeat-containing 5 (Birc5), also known as survivin, is a member of the inhibitor of apoptosis (IAP) family of proteins and regulates the size of tissues through cell division control. The uterus is the most dynamically sized organ among tissues during the estrous cycle. Although Birc5 is expressed in some terminally differentiated cells, the regulation of its expression in the uterus remains unknown. We investigated the regulation of Birc5 expression in the mouse uterus. RT-PCR analysis showed that Birc5 was expressed in various tissues, including the uterus; the expression level of Birc5 was significantly higher at the diestrus stage. Immunohistochemistry and Western blotting analysis revealed that Birc5 was more active in luminal and glandular epithelium than in endometrial stroma. In ovariectomized mice, Birc5 expression in the uterus was gradually increased by estrogen treatment; however, progesterone injection decreased its expression. Estrogen-induced Birc5 expression was blocked by treatment with estrogen receptor antagonist, ICI 182, 780 and progesterone-reduced Birc5 expression was inhibited by the progesterone receptor antagonist RU486. These results suggest that Birc5 expression is dynamically regulated by a combination of estrogen and progesterone via their receptor-mediated signaling.
Assuntos
Epitélio/metabolismo , Estro/genética , Survivina/genética , Útero/metabolismo , Animais , Estrogênios/metabolismo , Estro/metabolismo , Feminino , Camundongos , Camundongos Endogâmicos ICR , Progesterona/metabolismo , Survivina/metabolismo , Útero/citologia , Útero/fisiologiaRESUMO
The uterus is dynamically regulated in response to various signaling triggered by hormones during the estrous cycle. The Hippo signaling pathway is known as an important signaling for regulating cellular processes during development by balancing between cell growth and apoptosis. Serine/threonine protein kinase 3/4 (STK3/4) is a key component of the Hippo signaling network. However, the regulation of STK3/4-Hippo signaling in the uterus is little known. In this study, we investigated the regulation and expression of STK3/4 in the uterine endometrium during the estrous cycle. STK3/4 expression was dynamically regulated in the uterus during the estrous cycle. STK3/4 protein expression was gradually increased from the diestrus stage and reached the highest in the estrus stage. STK3/4 was exclusively localized in the luminal and glandular epithelial cells of the uterus, and phosphorylated STK3/4 was also increased at the estrus stage. Moreover, the increase of STK3/4 expression in uteri was induced by administration of estradiol, but not by progesterone injection in ovariectomized mice. Pretreatment with an estrogen receptor antagonist ICI 182,780 reduced estrogen-induced STK3/4 expression and its phosphorylation. The estrogen-induced STK3/4 expression was related to the increase in phosphorylation of downstream targets including LATS1/2 and YAP. These findings suggest that STK3/4-Hippo signaling acts a novel signaling pathway in the uterine epithelium and STK3/4-Hippo is one of key molecules for connecting between the estrogen downstream signaling pathway and the Hippo signaling pathway leading to regulate dynamic uterine epithelium during the estrous cycle.
Assuntos
Ciclo Estral/metabolismo , Proteínas Serina-Treonina Quinases/biossíntese , Animais , Apoptose/fisiologia , Proliferação de Células/fisiologia , Endométrio/metabolismo , Estradiol/farmacologia , Estrogênios/metabolismo , Ciclo Estral/fisiologia , Feminino , Camundongos , Camundongos Endogâmicos ICR , Fosforilação , Progesterona/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo , Receptores de Estrogênio/metabolismo , Serina-Treonina Quinase 3 , Transdução de Sinais/efeitos dos fármacos , Útero/metabolismoRESUMO
Spermatogenesis is a process by which haploid cells differentiate from germ cells in the seminiferous tubules of the testes. TLE3, a transcriptional co-regulator that interacts with DNA-binding factors, plays a role in the development of somatic cells. However, no studies have shown its role during germ cell development in the testes. Here, we examined TLE3 expression in the testes during spermatogenesis. TLE3 was highly expressed in mouse testes and was dynamically regulated in different cell types of the seminiferous tubules, spermatogonia, spermatids, and Sertoli cells, but not in the spermatocytes. Interestingly, TLE3 was not detected in Sertoli cells on postnatal day 7 (P7) but was expressed from P10 onward. The microarray analysis showed that the expression of numerous genes changed upon TLE3 knockdown in a Sertoli cell line TM4. These include 1597 up-regulated genes and 1452 down-regulated genes in TLE3-knockdown TM4 cells. Ingenuity Pathway Analysis (IPA) showed that three factors were up-regulated and two genes were down-regulated upon TLE3 knockdown in TM4 cells. The abnormal expression of the three factors is associated with cellular malfunctions such as abnormal differentiation and Sertoli cell formation. Thus, TLE3 is differentially expressed in Sertoli cells and plays a crucial role in regulating cell-specific genes involved in the differentiation and formation of Sertoli cells during testicular development.
Assuntos
Diferenciação Celular , Proteínas Correpressoras/metabolismo , Túbulos Seminíferos/metabolismo , Células de Sertoli/metabolismo , Espermatogênese , Testículo/metabolismo , Animais , Células Cultivadas , Proteínas Correpressoras/antagonistas & inibidores , Proteínas Correpressoras/genética , Regulação da Expressão Gênica no Desenvolvimento , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Interferente Pequeno/genética , Túbulos Seminíferos/citologia , Células de Sertoli/citologia , Testículo/citologiaRESUMO
The effect of 3, 4, 5-trimethoxy cinnamic acid (TMCA) against morphine-induced dependence in mice and rats was investigated. Mice were pretreated with TMCA and then morphine was injected intraperitoneally; whereas rats were treated with TMCA (i.p.) and infused with morphine into the lateral ventricle of brain. Naloxone-induced morphine withdrawal syndrome and conditioned place preference test were performed. Moreover, western blotting and immunohistochemistry were used to measure protein expressions. Number of naloxone-precipitated jumps and conditioned place preference score in mice were attenuated by TMCA. Likewise, TMCA attenuated morphine dependent behavioral patterns such as diarrhea, grooming, penis licking, rearing, teeth chattering, and vocalization in rats. Moreover, the expression levels of pNR1and pERK in the frontal cortex of mice and cultured cortical neurons were diminished by TMCA. In the striatum, pERK expression was attenuated despite unaltered expression of pNR1 and NR1. Interestingly, morphine-induced elevations of FosB/ΔFosB+ cells were suppressed by TMCA (50, 100 mg/kg) in the nucleus accumbens sub-shell region of mice. In conclusion, TMCA could be considered as potential therapeutic agent against morphine-induced dependence.
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Cinamatos/uso terapêutico , Dependência de Morfina/tratamento farmacológico , Dependência de Morfina/psicologia , Animais , Células Cultivadas , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Cinamatos/farmacologia , Condicionamento Psicológico/efeitos dos fármacos , Condicionamento Psicológico/fisiologia , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Dependência de Morfina/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Resultado do TratamentoRESUMO
We investigated the effects of flumazenil, aminophylline, and ephedrine on the excitatory amino acid transporter type 3 (EAAT3) activity and the interaction with propofol. EAAT3 was expressed in the Xenopus oocytes. L-Glutamate-induced membrane currents were measured using the two-electrode voltage clamp at various drug concentrations. Oocytes were preincubated with protein kinase C- (PKC-) activator, or inhibitor, and phosphatidylinositol 3-kinase (PI3K) inhibitor. To study the interaction with propofol, oocytes were exposed to propofol, propofol + aminophylline, or ephedrine. Aminophylline and ephedrine significantly decreased EAAT3 activity. Aminophylline (95 µM) and ephedrine (1.19 µM) significantly decreased Vmax, but not Km of EAAT3, for glutamate. The phorbol 12-myristate-13-acetate-induced increase in EAAT3 activity was abolished by aminophylline or ephedrine. The decreased EAAT3 activities by PKC inhibitors (staurosporine, chelerythrine) and PI3K inhibitor (wortmannin) were not significantly different from those by aminophylline or ephedrine, as well as those by PKC inhibitors or PI3K inhibitor + aminophylline or ephedrine. The enhanced EAAT3 activities induced by propofol were significantly abolished by aminophylline or ephedrine. Aminophylline and ephedrine inhibit EAAT3 activity via PKC and PI3K pathways and abolish the increased EAAT3 activity by propofol. Our results indicate a novel site of action for aminophylline and ephedrine.
Assuntos
Transportador 3 de Aminoácido Excitatório/genética , Oócitos/efeitos dos fármacos , Propofol/farmacologia , Xenopus laevis/genética , Aminofilina/farmacologia , Animais , Efedrina/farmacologia , Flumazenil/farmacologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Oócitos/crescimento & desenvolvimento , Técnicas de Patch-Clamp , Fosfatidilinositol 3-Quinases/genética , Proteína Quinase C/genética , Inibidores de Proteínas Quinases/farmacologia , Xenopus laevis/crescimento & desenvolvimentoRESUMO
BACKGROUND/AIMS: Cyclic adenosine monophosphate (cAMP)-dependent type 2 regulatory subunit beta (Prkar2b) is a regulatory isoform of cAMP-dependent protein kinase (PKA), which is the primary target for cAMP actions. In oocytes, PKA and the pentose phosphate pathway (PPP) have important roles during the germinal vesicle (GV) stage arrest of development. Although the roles of the PKA signal pathway have been studied in the development of oocyte, there has been no report on the function of PRKAR2B, a key regulator of PKA. METHODS: Using reverse transcription polymerase chain reaction (RT-PCR), quantitative real-time PCR (qRT-PCR), immunohistochemistry, and immunofluorescence, we determined the relative expression of Prkar2b in various tissues, including ovarian follicles, during oocyte maturation. Prkar2b-interfering RNA (RNAi) microinjection was conducted to confirm the effect of Prkar2b knockdown, and immunofluorescence, qRT-PCR, and time-lapse video microscopy were used to analyze Prkar2b-deficient oocytes. RESULTS: Prkar2b is strongly expressed in the ovarian tissues, particularly in the growing follicle. During oocyte maturation, the highest expression of Prkar2b was during metaphase I (MI), with a significant decrease at metaphase II (MII). RNAi-mediated Prkar2b suppression resulted in MI-stage arrest during oocyte development, and these oocytes exhibited abnormal spindle formation and chromosome aggregation. Expression of other members of the PKA family (except for Prkaca) were decreased, and the majority of the PPP factors were also reduced in Prkar2b-deficient oocytes. CONCLUSION: These results suggest that Prkar2b is closely involved in the maturation of oocytes by controlling spindle formation and PPP-mediated metabolism.
Assuntos
Subunidade RIIbeta da Proteína Quinase Dependente de AMP Cíclico/metabolismo , Interferência de RNA , Animais , Subunidade RIIbeta da Proteína Quinase Dependente de AMP Cíclico/antagonistas & inibidores , Subunidade RIIbeta da Proteína Quinase Dependente de AMP Cíclico/genética , Proteínas Quinases Dependentes de AMP Cíclico/genética , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Feminino , Metáfase , Camundongos , Camundongos Endogâmicos ICR , Microscopia de Fluorescência , Microscopia de Vídeo , Oócitos/crescimento & desenvolvimento , Oócitos/metabolismo , Oogênese , Folículo Ovariano/metabolismo , Folículo Ovariano/patologia , RNA de Cadeia Dupla/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Imagem com Lapso de TempoRESUMO
OBJECTIVE To evaluate dynamic movement of the diaphragm of clinically normal dogs by use of fluoroscopy and to obtain quantitative data of diaphragmatic excursion during spontaneous breathing. ANIMALS 8 healthy male Beagles with no history of respiratory tract disease. PROCEDURES Fluoroscopy was performed during stabilized respiratory conditions. The beam center was located at the level of the diaphragm, and diaphragmatic motion was recorded during 3 respiratory cycles in dogs positioned in left lateral, right lateral, and dorsal recumbency. Extent of excursion of the diaphragmatic cupula and both crura, difference in excursion between the left and right crura, and ratios of the excursions of the diaphragmatic cupula and left and right crura to the length of the eighth thoracic vertebra were determined. RESULTS Diaphragmatic crural excursion was symmetric for dogs in right lateral recumbency, and the crural excursion was approximately three-quarters of the vertebral length; however, crural excursion appeared to be asymmetric for dogs in left lateral recumbency. Mean ± SD difference in excursion between the right and left crura was 22.68 ± 8.68% for left lateral recumbency, 16.63 ± 9.22% for right lateral recumbency, and 18.11 ± 12.96% for dorsal recumbency. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that the fluoroscopic view of a dog positioned in right lateral recumbency may allow better evaluation of the symmetry of diaphragmatic excursion, compared with results for other recumbency positions. This study provided quantitative data on the excursion of diaphragmatic movement observed by use of fluoroscopy in clinically normal Beagles.
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Diafragma/fisiologia , Cães/fisiologia , Fluoroscopia/veterinária , Respiração , Animais , Masculino , Movimento , Esforço FísicoRESUMO
Premature ovarian failure during chemotherapy is a serious problem for young women with cancer. To preserve the fertility of these patients, approaches to prevent chemotherapy-induced ovarian failure are needed. In a previous study, we reported that melatonin treatment prevents the depletion of the dormant follicle pool via repression of the simultaneous activation of dormant primordial follicles by cisplatin. However, melatonin's protective effect was only partial and thus insufficient. In this study, we found that the hormone ghrelin enhances the protective effect of melatonin against cisplatin-induced ovarian failure in mouse model. Co-administration of melatonin and ghrelin more effectively prevented cisplatin-induced follicle disruption. Simultaneous treatment with melatonin and ghrelin almost restored the number of primordial follicles and the corpus luteum in cisplatin-treated ovaries, compared with single administration. We found melatonin and ghrelin receptors on the cell membrane of premature oocytes of primordial follicles. In addition, melatonin and ghrelin co-administration inhibited the cisplatin-induced phosphorylation of PTEN and FOXO3a that induces cytoplasmic translocation of FOXO3a. Inhibition of FOXO3a phosphorylation by melatonin and ghrelin increased the binding affinity of FOXO3a for the p27Kip1 promoter in primordial follicles. Co-administration of melatonin and ghrelin in cisplatin-treated ovaries restored the expression of p27Kip1 , which is critical for retention of the dormant status of primordial follicles. In conclusion, these findings suggest that melatonin and ghrelin co-administration is suitable for use as a fertoprotective adjuvant therapy during cisplatin chemotherapy in young female cancer patients.
Assuntos
Antioxidantes/uso terapêutico , Grelina/uso terapêutico , Melatonina/uso terapêutico , Ovário/efeitos dos fármacos , Insuficiência Ovariana Primária/prevenção & controle , Animais , Antineoplásicos/efeitos adversos , Antioxidantes/farmacologia , Cisplatino/efeitos adversos , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada , Feminino , Proteína Forkhead Box O3/metabolismo , Grelina/farmacologia , Humanos , Melatonina/farmacologia , Camundongos Endogâmicos ICR , Ovário/metabolismo , Insuficiência Ovariana Primária/induzido quimicamente , Receptores de Grelina/metabolismo , Receptores de Melatonina/metabolismoRESUMO
Despite accumulating evidence of physiological abnormalities related to posttraumatic stress disorder (PTSD), the current diagnostic criteria for PTSD still rely on clinical interviews. In this study, we investigated the diagnostic potential of multimodal neuroimaging for identifying posttraumatic symptom trajectory after trauma exposure. Thirty trauma-exposed individuals and 29 trauma-unexposed healthy individuals were followed up over a 5-year period. Three waves of assessments using multimodal neuroimaging, including structural magnetic resonance imaging (MRI) and diffusion-weighted MRI, were performed. Based on previous findings that the structural features of the fear circuitry-related brain regions may dynamically change during recovery from the trauma, we employed a machine learning approach to determine whether local, connectivity, and network features of brain regions of the fear circuitry including the amygdala, orbitofrontal and ventromedial prefrontal cortex (OMPFC), hippocampus, insula, and thalamus could distinguish trauma-exposed individuals from trauma-unexposed individuals at each recovery stage. Significant improvement in PTSD symptoms was observed in 23%, 52%, and 88% of trauma-exposed individuals at 1.43, 2.68, and 3.91 years after the trauma, respectively. The structural features of the amygdala were found as major classifiers for discriminating trauma-exposed individuals from trauma-unexposed individuals at 1.43 years after the trauma, but these features were nearly normalized at later phases when most of the trauma-exposed individuals showed clinical improvement in PTSD symptoms. Additionally, the structural features of the OMPFC showed consistent predictive values throughout the recovery period. In conclusion, the current study provides a promising step forward in the development of a clinically applicable predictive model for diagnosing PTSD and predicting recovery from PTSD.
Assuntos
Encéfalo/diagnóstico por imagem , Imagem Multimodal/métodos , Neuroimagem/métodos , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Adolescente , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Adulto JovemRESUMO
AIMS/HYPOTHESIS: Overweight and obesity may significantly worsen glycaemic and metabolic control in type 2 diabetes. However, little is known about the effects of overweight and obesity on the brains of people with type 2 diabetes. Here, we investigate whether the presence of overweight or obesity influences the brain and cognitive functions during early stage type 2 diabetes. METHODS: This study attempted to uncouple the effects of overweight/obesity from those of type 2 diabetes on brain structures and cognition. Overweight/obese participants with type 2 diabetes had more severe and progressive abnormalities in their brain structures and cognition during early stage type 2 diabetes compared with participants with normal weight. Relationships between each of these measures and disease duration were also examined. RESULTS: Global mean cortical thickness was lower in the overweight/obese type 2 diabetes group than in the normal-weight type 2 diabetes group (z = -2.96, p for group effect = 0.003). A negative correlation was observed between disease duration and global mean white matter integrity (z = 2.42, p for interaction = 0.02) in the overweight/obese type 2 diabetes group, but not in the normal-weight type 2 diabetes group. Overweight/obese individuals with type 2 diabetes showed a decrease in psychomotor speed performance related to disease duration (z = -2.12, p for interaction = 0.03), while normal-weight participants did not. CONCLUSIONS/INTERPRETATION: The current study attempted to uncouple the effects of overweight/obesity from those of type 2 diabetes on brain structures and cognition. Overweight/obese participants with type 2 diabetes had more severe and progressive abnormalities in brain structures and cognition during early stage type 2 diabetes compared with normal-weight participants.
Assuntos
Encéfalo/patologia , Diabetes Mellitus Tipo 2/fisiopatologia , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Adulto , Glicemia , Índice de Massa Corporal , Peso Corporal , Encéfalo/diagnóstico por imagem , Estudos de Casos e Controles , Cognição , Transtornos Cognitivos/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Feminino , Substância Cinzenta/patologia , Humanos , Resistência à Insulina , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Sobrepeso/complicações , Substância Branca/patologiaRESUMO
This study evaluated whether renal perfusion changes can be noninvasively estimated by using contrast-enhanced ultrasonography (CEUS) in renal ischemia-reperfusion injury and investigated the correlation between renal perfusion measured by CEUS and necrosis and apoptosis of renal tubular epithelial cells. In six dogs with experimentally induced renal ischemia-reperfusion injury, changes in time to peak intensity, peak intensity, and area under the curve were measured on CEUS. Peak intensity and area under the curve of the renal cortex began to decrease on day 1 (about 20% lower than baseline) and reached the lowest levels (about 50% of baseline) on day 4. They then gradually increased until day 10, at which time peak intensity was about 87% and area under the curve was about 95% of baseline; neither fully recovered. Both parameters were strongly correlated with the necrosis scores on histopathologic examination on day 4 (r = -0.810 of peak intensity and r = -0.886 of area under the curve). CEUS allowed quantitative evaluation of perfusion changes in acute renal ischemia-reperfusion injury, and CEUS results were correlated with renal tubular damage on histopathologic examination. Thus, CEUS could be a noninvasive, quantitative diagnostic method for determining progress of renal ischemia-reperfusion injury.
Assuntos
Doenças do Cão/diagnóstico por imagem , Córtex Renal/diagnóstico por imagem , Medula Renal/diagnóstico por imagem , Tecido Parenquimatoso/diagnóstico por imagem , Traumatismo por Reperfusão/veterinária , Ultrassonografia/veterinária , Animais , Apoptose , Meios de Contraste/química , Cães , Túbulos Renais/diagnóstico por imagem , Masculino , Necrose/diagnóstico por imagem , Necrose/veterinária , Traumatismo por Reperfusão/diagnóstico por imagemRESUMO
OBJECTIVE To evaluate effects of position, time in that position, and positive end-expiratory pressure on ground-glass opacity caused by physiologic atelectasis on lung CT images and to determine effects of recumbency position before CT. ANIMALS 6 healthy Beagles. PROCEDURES In a crossover study, dogs were placed in 4 positions (sternal, dorsal, right lateral, and left lateral recumbency) for 2 holding times (30 and 60 minutes). Dogs were then repositioned in sternal recumbency, and CT was performed at 2 positive end-expiratory pressures (0 and 15 mm Hg). Location, distribution, and degree of ground-glass opacities were evaluated on lung CT images. Volume and mean density of the lungs and ground-glass opacities as well as maximum density of ground-glass opacities were evaluated. RESULTS Ground-glass opacities were mainly observed in parts of the lungs that were dependent during the various positions before CT, except for sternal recumbency. Opacities were reversible and decreased or disappeared after lung inflation. Ground-glass opacities were observed most frequently and had greatest severity when dogs were positioned in left lateral recumbency before CT. Ground-glass opacities were negligible for dogs positioned in sternal recumbency before CT. CONCLUSIONS AND CLINICAL RELEVANCE Location and reversibility of ground-glass opacities may help clinicians distinguish whether they are attributable to atelectasis or a result of pathological changes. Dogs should be positioned in sternal recumbency to minimize the occurrence of ground-glass opacities, particularly when several procedures are performed before CT, which increases the time that a dog will remain in the same position.
Assuntos
Pulmão/diagnóstico por imagem , Posicionamento do Paciente/veterinária , Atelectasia Pulmonar/veterinária , Tomografia Computadorizada por Raios X/veterinária , Animais , Estudos Cross-Over , Cães , Masculino , Posicionamento do Paciente/normas , Respiração com Pressão Positiva , Atelectasia Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X/normasRESUMO
OBJECTIVE To assess by use of various diagnostic imaging modalities acute changes in livers of healthy dogs after radiofrequency ablation (RFA) and determine the capability of each imaging modality to monitor ablation lesion changes. ANIMALS 6 healthy Beagles. PROCEDURES 12 ablation lesions were created in the liver of the dogs (2 lesions/dog). Ablation lesions were evaluated by use of conventional ultrasonography, strain elastography, and contrast-enhanced ultrasonography immediately after (time 0), 30 to 60 minutes after, and 3 days after RFA, and by use of CT 30 minutes and 3 days after RFA. Three dogs were euthanized shortly after RFA, and the other 3 dogs were euthanized on day 3. Lesion size measured by each imaging modality was compared with necropsy findings. RESULTS Immediately after RFA, clear margins were more visible with elastography and contrast-enhanced ultrasonography than with conventional ultrasonography, which had acoustic shadowing. On triphasic contrast CT, the ablation zone, which indicated necrosis and hemorrhage, was not enhanced and could be measured. Marked enhancement of the periablation rim was observed during the venous phase and was identified as granulation tissue. Size of the ablation area measured on enhanced CT images was strongly correlated with actual lesion size. CONCLUSIONS AND CLINICAL RELEVANCE For dogs of this study, CT was the most reliable method for lesion size determination. Although ultrasonographic imaging measurements underestimated lesion size, all modalities could be used to provide additional real-time guidance for RFA procedures of the liver as well as for other RFA procedures.
Assuntos
Técnicas de Imagem por Elasticidade , Fígado/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Ultrassonografia , Animais , Ablação por Cateter , Cães , Feminino , Hemorragia/diagnóstico por imagem , Fígado/patologia , Masculino , Necrose/diagnóstico por imagemRESUMO
Dexamethasone-induced RAS-related protein 1 (RASD1) is a signaling protein that is involved in various cellular processes. In a previous study, we found that RASD1 expression was down-regulated in the uterine endometrium of repeated implantation failure patients. The study aim was to determine whether RASD1 is expressed in the endometrium of mouse uterus and how it is regulated by steroid hormones during the estrous cycle. In this study, we investigated RASD1 expression and regulation in an ovariectomized female mouse model. Rasd1 mRNA was highly expressed in mouse reproductive tissues, including the uterus. Rasd1 expression was detected exclusively in the endometrial epithelium at the proestrus stage of the estrous cycle. Rasd1 expression in uteri increased with administration of estradiol, but not progesterone. Its expression was rapidly induced within 2 h after E2 treatment. Pretreatment with ICI 182,780, an estrogen receptor antagonist, reduced RASD1 protein expression. In addition, we identified that rapid expression of Rasd1 was mediated by the estrogen intracellular signaling including both p38-mitogen-activated protein kinase and the extracellular signal-regulated kinase. These findings suggest that RASD1 acts as a novel signaling molecule and plays an important role in regulating dynamic uterine remodeling during the estrous cycle in the uterus.